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Landmark Trials

Fabio Mangiacapra, Edoardo Bressi, Alessandro Sticchi, Carmine Morisco, Emanuele Barbato
The presence and extent of myocardial ischemia are the major determinants of prognosis in patients with coronary artery disease (CAD). Unlike coronary angiography alone, fractional flow reserve (FFR) has enabled interventional cardiologists to accurately determine whether coronary atherosclerotic plaques are responsible for myocardial ischemia, and therefore deserve to be revascularized. Areas covered: An overview on the role of FFR in the diagnosis and treatment of coronary artery disease, as well as the potential related controversies is provided...
June 20, 2018: Expert Review of Cardiovascular Therapy
Leena Halim, Adam Ajina, John Maher
Following the landmark approvals by the United States Food and Drug Administration, the adoptive transfer of CD19-directed chimeric antigen receptor (CAR) T-cells has now entered mainstream clinical practice for patients with chemotherapy-resistant or refractory B-cell malignancies. These approvals have followed on from a prolonged period of pre-clinical evaluation, informing the design of clinical trials that have demonstrated unprecedented efficacy in this difficult to treat patient population. However, the delivery of autologous CAR-engineered T-cell therapy is complex, costly and not without significant risk...
June 2018: Best Practice & Research. Clinical Haematology
Barry Danby Michael
This Commentary focuses on the landmark paper about hypoxia in radiotherapy by Gray, Scott et al published in 1953. By then, it was known that hypoxic regions in tumours could make them resistant to radiation treatment and that this was a possible cause of failure. The paper proposed that oxygen breathing could substantially decrease this resistance without incurring significant additional damage to normal tissues, thus reducing the likelihood of recurrence. Although the paper's supporting data were in some respects incomplete, the case it made was convincing and it prompted pilot clinical trials that combined radiotherapy with oxygen breathing, including under elevated pressure...
June 15, 2018: British Journal of Radiology
Vera Hirsh, Yin Wan, Fang-Ju Lin, Sandra Margunato-Debay, Teng Jin Ong, Marc Botteman, Corey Langer
BACKGROUND: First-line nab-paclitaxel/carboplatin was associated with a significantly improved overall response rate (primary endpoint) versus paclitaxel/carboplatin in a phase III trial of advanced non-small-cell lung cancer (NSCLC). We report the results of an analysis evaluating the correlation of response and the time to response with survival and quality-adjusted outcomes. PATIENTS AND METHODS: Using a landmark approach, progression-free survival (PFS), overall survival (OS), and quality-adjusted time without symptoms or toxicity (Q-TWiST) were compared between patients with a confirmed partial or complete response at or before 6 weeks (≤ 6-week responders) and those without (≤ 6-week nonresponders)...
May 7, 2018: Clinical Lung Cancer
Yan Xu, Chuanpu Hu, Yanli Zhuang, Benjamin Hsu, Zhenhua Xu, Amarnath Sharma, Honghui Zhou
To characterize the dose-exposure-response relationship of sirukumab, an anti-interleukin 6 human monoclonal antibody, in the treatment of moderately to severely active rheumatoid arthritis (RA), we conducted exposure-response (E-R) modeling analyses based on data from two pivotal phase 3 placebo-controlled trials of sirukumab in patients with RA who were inadequate responders to nonbiologic disease-modifying antirheumatic drugs or anti-tumor necrosis factor α agents. A total of 2176 patients were included for the analyses and received subcutaneous administration of either placebo or sirukumab 50 mg every 4 weeks or 100 mg every 2 weeks...
June 14, 2018: Journal of Clinical Pharmacology
Meta Roestenberg, Marie-Astrid Hoogerwerf, Daniela M Ferreira, Benjamin Mordmüller, Maria Yazdanbakhsh
Controlled human infection (CHI) trials, in which healthy volunteers are experimentally infected, can accelerate the development of novel drugs and vaccines for infectious diseases of global importance. The use of CHI models is expanding from around 60 studies in the 1970s to more than 120 publications in this decade, primarily for influenza, rhinovirus, and malaria. CHI trials have provided landmark data for several registered drugs and vaccines, and have generated unprecedented scientific insights. Because of their invasive nature, CHI studies demand critical ethical review according to established frameworks...
June 8, 2018: Lancet Infectious Diseases
Anna-Maria Larsson, Sara Jansson, Pär-Ola Bendahl, Charlotte Levin Tykjaer Jörgensen, Niklas Loman, Cecilia Graffman, Lotta Lundgren, Kristina Aaltonen, Lisa Rydén
BACKGROUND: Circulating tumor cells (CTCs) carry independent prognostic information in patients with metastatic breast cancer (MBC) on different lines of therapy. Moreover, CTC clusters are suggested to add prognostic information to CTC enumeration alone but their significance is unknown in patients with newly diagnosed MBC. We aimed to evaluate whether longitudinal enumeration of circulating tumor cells (CTCs) and CTC clusters could improve prognostication and monitoring of patients with metastatic breast cancer (MBC) starting first-line therapy...
June 8, 2018: Breast Cancer Research: BCR
Matteo Lambertini, Christine Campbell, José Bines, Larissa A Korde, Miguel Izquierdo, Debora Fumagalli, Lucia Del Mastro, Michail Ignatiadis, Kathleen Pritchard, Antonio C Wolff, Christian Jackisch, Istvan Lang, Michael Untch, Ian Smith, Frances Boyle, Binghe Xu, Carlos H Barrios, José Baselga, Alvaro Moreno-Aspitia, Martine Piccart, Richard D Gelber, Evandro de Azambuja
Background: In premenopausal patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer, the gonadotoxicity of trastuzumab and lapatinib remains largely uncertain, and the prognostic effect of treatment-related amenorrhea (TRA) is unknown. Methods: In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (BIG 2-06) phase III trial, HER2-positive early breast cancer patients were randomized (1:1:1:1) to receive one year of trastuzumab, lapatinib, their sequence, or their combination...
June 5, 2018: Journal of the National Cancer Institute
Rahul Mukherjee, Raffaella Nenna, Alice Turner
The landmark YONIV trial addressed key practical questions surrounding the early use of ward-based noninvasive ventilation, which is now an established evidence-based treatment for acute hypercapnic respiratory failure
June 2018: Breathe
Carolina Lavazza, Valeria Milano, Alessandra Abenavoli, Alberto Maggiani
INTRODUCTION: Accurate and reliable palpation is needed to identify anatomical landmarks as well as to assess motion and dysfunctions. Although different trials suggested that training might increase reliability of palpation, the poor dependability of the examined tests may show the need to review the teaching methods to improve palpatory accuracy? The aims of this study were: METHODS: 82 examiners with different years of experience were enrolled from AIMO institute. Two different type of training sessions were performed (individual and group training)...
April 2018: Journal of Bodywork and Movement Therapies
Francisco Xavier de Araujo, Maurício Scholl Schell, Giovanni Esteves Ferreira, Mariana Della Valentina Pessoa, Luiza Raulino de Oliveira, Brian Giacomini Borges, Fabrício Edler Macagnan, Rodrigo Della Méa Plentz, Marcelo Faria Silva
OBJECTIVE: To compare the effects of two different mobilization techniques and a placebo intervention applied to the thoracic spine on heart rate variability (HRV) and pressure pain threshold (PPT) in asymptomatic individuals. METHODS: Sixty healthy asymptomatic subjects aged between 18 and 40 years old were randomized to a single session of one of the three interventions: posterior-to-anterior (PA) rotatory thoracic passive accessory intervertebral mobilization (PAIVM) (PA group), unilateral thoracic PA in slump position (SLUMP group) or placebo intervention (Placebo group)...
April 2018: Journal of Bodywork and Movement Therapies
Jason Nogic, Yi-Wei Baey, Nitesh Nerlekar, Francis J Ha, James D Cameron, Arthur Nasis, Nick E J West, Adam J Brown
BACKGROUND: Polymer-free drug eluting stents (PF-DES) were developed, in part, to overcome risk of late ischemic events observed with permanent polymer-coated DES (PP-DES). However, trial results are inconsistent with longer-term safety and efficacy of PF-DES remaining unknown. We performed a meta-analysis of randomized trials assessing outcomes of patients receiving PF-DES versus PP-DES for treatment of coronary artery disease (CAD). METHODS: Electronic searches were performed for randomized trials comparing outcomes between PF-DES and PP-DES...
May 24, 2018: Journal of Interventional Cardiology
Kirsten B Goldberg, Gideon M Blumenthal, Richard Pazdur
The Food and Drug Administration formally established the Oncology Center of Excellence (OCE) in January 2017, as authorized by the 21st Century Cures Act, to expedite the development and review of certain drugs, biologics, and devices for the treatment of cancer. In its first year, the OCE conducted the clinical reviews for several products, including the first 2 chimeric antigen receptor T-cell therapies approved for the treatment of advanced hematologic malignancies and an in vitro diagnostic next-generation sequencing panel, FoundationOne CDx...
May 2018: Cancer Journal
Richard D Branson
Long-term oxygen therapy (LTOT) at home has been demonstrated to improve survival in patients with COPD and severe resting hypoxemia. Support for LTOT is based on 2 landmark trials published nearly 4 decades ago. These results form the basis for reimbursement and prescription of LTOT to this day. Recent work has demonstrated no outcome benefit of LTOT in stable COPD patients with moderate desaturation at rest or during activity. Oxygen therapy during activity and exercise has been shown to alleviate symptoms and maintain arterial oxygen saturation, but not improve long-term outcomes...
June 2018: Respiratory Care
Marlies M Kok, Paolo Zocca, Rosaly A Buiten, Peter W Danse, Carl E Schotborgh, Martijn Scholte, Marc Hartmann, Martin G Stoel, Gert van Houwelingen, Gerard C M Linssen, Carine J M Doggen, Clemens von Birgelen
AIMS: The aim of the study was to evaluate the two-year clinical outcome of all-comer trial participants who were treated with two very different thin-strut biodegradable polymer versus thin-strut durable polymer drug-eluting stents (DES). Prolonged clinical outcome after discontinuation of dual antiplatelet therapy is of particular interest, given the highly dissimilar polymer types, amount, distribution, and degradation speed of both biodegradable polymer DES. METHODS AND RESULTS: The BIO-RESORT trial (NCT01674803) randomly assigned 3,514 patients to treatment with biodegradable polymer SYNERGY everolimus-eluting stents (EES) or Orsiro sirolimus-eluting stents (SES), or durable polymer Resolute Integrity zotarolimus-eluting stents (ZES)...
May 23, 2018: EuroIntervention
Johan Svanerud, Jung-Min Ahn, Allen Jeremias, Marcel van 't Veer, Ankita Gore, Akiko Maehara, Aaron Crowley, Nico H J Pijls, Bernard De Bruyne, Nils P Johnson, Barry Hennigan, Stuart Watkins, Colin Berry, Keith G Oldroyd, Seung-Jung Park, Ziad A Ali
AIMS: Randomised controlled trials have reported instantaneous wave-free ratio (iFR) to be non-inferior to fractional flow reserve (FFR) for major adverse cardiovascular events at one year; however, iFR is limited by sensitive landmarking of the pressure waveform, and the assumption that maximal flow and minimal resistance occur during a fixed period of diastole. We sought to validate the resting full-cycle ratio (RFR), a novel non-hyperaemic index of coronary stenosis severity based on unbiased identification of the lowest distal coronary pressure to aortic pressure ratio (Pd/Pa), independent of the ECG, landmark identification, and timing within the cardiac cycle...
May 23, 2018: EuroIntervention
Sebron Harrison, Brendon Stiles, Nasser Altorki
Since 1995, lobar resection became the standard of care for medically fit patients with early stage lung cancer. This was based on the results of a single randomized trial comparing lobectomy and sublobar resection (SLR) in stage I lung cancer conducted by the lung cancer study group between 1982 and 1988. The conclusions of the study included a statistically significant tripling in loco-regional recurrence (LR) after limited resection but no difference between the two arms of the trial in systemic recurrence...
April 2018: Journal of Thoracic Disease
Abhi Pandhi, Georgios Tsivgoulis, Nitin Goyal, Muhammad F Ishfaq, Shailesh Male, Efstathios Boviatsis, Jason J Chang, Ramin Zand, Konstantinos Voumvourakis, Lucas Elijovich, Anne W Alexandrov, Marc D Malkoff, Daniel Hoit, Adam S Arthur, Andrei V Alexandrov
BACKGROUND AND PURPOSE: Despite recent landmark randomized controlled trials showing significant benefits for hemicraniectomy (HCT) compared with medical therapy (MT) in patients with malignant middle cerebral artery infarction (MMCAI), HCT rates have not substantially increased in the United States. We sought to evaluate early outcomes in patients with MMCAI who were treated with HCT (cases) in comparison to patients treated with MT due to the perception of procedural futility by families (controls)...
May 15, 2018: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
Carla J Greenbaum, Cate Speake, Jeffrey Krischer, Jane Buckner, Peter A Gottlieb, Desmond A Schatz, Kevan C Herold, Mark A Atkinson
The early to mid-1980s were an inflection point in the history of type 1 diabetes research. Two landmark events occurred: the initiation of immune-based interventions seeking to prevent type 1 diabetes and the presentation of an innovative model describing the disorder's natural history. Both formed the basis for hundreds of subsequent studies designed to achieve a dramatic therapeutic goal-a means to prevent and/or reverse type 1 diabetes. However, the need to screen large numbers of individuals and prospectively monitor them using immunologic and metabolic tests for extended periods of time suggested such efforts would require a large collaborative network...
May 16, 2018: Diabetes
Abhinav Sharma, Christopher P Cannon, William B White, Yuyin Liu, George L Bakris, William C Cushman, Faiez Zannad
BACKGROUND: Antihyperglycemic therapies may increase the risk of cardiovascular events including hospitalization for heart failure. There is a paucity of data evaluating the cardiovascular safety of antihyperglycemic therapies in the high-risk period following an acute coronary syndrome (ACS). METHODS AND RESULTS: The EXAMINE (Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care) trial randomized 5380 patients who were 15 to 90 days post ACS to the dipeptidyl dipeptidase-IV (DPP-IV) inhibitor alogliptin versus placebo; mean follow-up was 18 months...
May 16, 2018: Journal of the American Heart Association
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